The Muscular Dystrophy Association recently awarded an MDA clinical research network grant to Nicholas Johnson, vice chair of research and associate professor of neurology at Virginia Commonwealth University in Richmond, to establish the Limb-Girdle Muscular Dystrophy (LGMD) Clinical Research Network.

The investment, totaling $700,000 over two years, supports seven centers with expertise in LGMD research and clinical care and is targeted to facilitate the development of tools and infrastructure needed to efficiently and effectively conduct clinical trials and accelerate treatments for LGMDs.

An urgent need for clinical trial readiness

LGMDs are a diverse group of disorders with many subtypes categorized by disease gene and mode of inheritance. The unifying features of LGMDs are weakness and atrophy of the limb-girdle muscles (those around the hips and shoulders). However, the age at which symptoms appear, and the speed and severity of disease progression, can vary. There are no available treatments for any of the LGMD subtypes.

Therapy development in LGMDs can significantly benefit from rich natural history data to describe the clinical course of the different forms of LGMD, as well as from validated clinical outcome assessments that can be used to determine whether a drug or intervention has provided treatment benefit.

Through the coordinated activities and enhanced communication among this new network of LGMD clinics, Johnson and colleagues aim to standardize approaches and develop the clinical outcome assessments to be used in future clinical trials.

“MDA is pleased to support the development and work of the LGMD Clinical Research Network, which will put in place critical infrastructure for limb-girdle muscular dystrophy research and therapy development,” says MDA Scientific Program Officer Lianna Orlando, Ph.D. “The network is well-suited to address current challenges facing LGMD researchers and clinicians, and its work will improve clinical trial readiness in this group of diseases.”

Critical preparation for clinical trials

An initial step in the development of the network infrastructure is to conduct a longitudinal study of candidate clinical outcome assessments and develop disease-specific patient-reported outcomes. Investigators will initially focus on four different genetic LGMD subtypes and will collect DNA, genetic diagnosis and clinical information to help characterize the natural course of the disease.

“We believe that the absence of tools to measure disease progression is a major barrier to conducting drug trials in this underserved population,” Johnson says. “This is critically important given the exciting progress in gene therapy.

“We are focused on developing these tools, with a particular focus on those assessments that may be used across different LGMD types, and which assessments are unique to specific subtypes,” Johnson adds. “Progress in these areas is best suited for a research network that is geographically distributed and includes investigators with varied expertise in clinical and laboratory methods.”

The network comprises seven medical centers with significant expertise in LGMD research and clinical care, spanning across the United States. Centers are:

California: University of California-Irvine — Tasheen Mozzaffar, M.D., site investigator

Colorado: University of Colorado in Aurora — Matt Wicklund, M.D., site investigator

Iowa: University of Iowa in Iowa City — Kathy Mathews, M.D., site investigator

MDA has funded more than $59 million in LGMD research since 1950, and including this most recent award, currently is funding 10 active LGMD grants, with a total funding commitment of more than $2.8 million.

The new grant was approved by MDA’s Board of Directors after careful deliberations and analysis by MDA advisors and research staff. Currently, MDA is funding 177 research projects around the world, with another 28 pending.